Studies on complex biological phenomena often combine two or more imaging techniques to collect high-quality comprehensive data directly in situ, preserving the biological context. Mass spectrometry imaging (MSI) and vibrational spectroscopy imaging (VSI) complement each other in terms of spatial resolution and molecular information. In the past decade, several combinations of such multimodal strategies arose in research fields as diverse as microbiology, cancer, and forensics, overcoming many challenges toward the unification of these techniques. Here we focus on presenting the advantages and challenges of multimodal imaging from the point of view of studying biological samples as well as giving a perspective on the upcoming trends regarding this topic. The latest efforts in the field are discussed, highlighting the purpose of the technique for clinical applications.